CELLS FROM MOTHER CAN BOOST SUCCESS OF SIBLING-TO-SIBLING KIDNEY TRANSPLANTS, UW STUDY FINDS
MADISON -- Kidney transplants between siblings with slightly different tissue types are as much as 28 percent more likely to survive long-term when maternal tissue types are used to determine the donor, a new study from the University of Wisconsin Medical School suggests.
The research suggests that a small change in organ selection could boost long term success rates for slightly mismatched transplants to equal that of the ideal donor, an identically matched sibling, according to William Burlingham, Ph.D., a UW Medical School transplant scientist. The study, prompted by a kidney recipient who showed surprising transplant tolerance without anti-rejection drugs, is described by Burlingham in the Dec. 3 edition of the New England Journal of Medicine.
Researchers studied records for 205 people who received a kidney from a brother or sister at nine transplant centers in the United States and the Netherlands. Kidneys from siblings with maternal tissue types were 19 and 28 percent more likely to survive five and 10 years after transplantation, respectively, than kidneys from siblings with paternal traits, according to the team's findings. Those results closely parallel success rates for perfectly matched, or HLA-identical, transplants.
"Simply adding maternal HLA typing (or paternal typing if the mother is unavailable) to the routine family workup for living-related kidney donation will expand the pool of optimal donors, giving transplant surgeons a viable alternative when no HLA-identical sibling is available," said Burlingham, a UW Medical School assistant professor of surgery, pathology and laboratory medicine. The research may also aid in unrelated kidney donations and stem cell transplants.
Kidneys are the most frequently transplanted organs. The 12,300 kidneys transplanted during 1997 comprised nearly 59 percent of U.S. transplants. In 1996, the last year for which full figures are available, 7 in 10 transplanted kidneys came from cadaveric donors. Sibling-to-sibling transplants accounted for about 41 percent of the 3,300 living donors.
Transplant centers perform tissue typing in an attempt to find the most compatible donors and recipients. In a kidney transplant, a "perfect" match means that all six key HLA antigens -- proteins on the surface of cells -- match between donor and recipient. Fewer antigen matches mean a greater chance that the recipient's immune system may reject the transplanted organ.
The benefit of maternally matched organs may relate to "cellular priming," a favorable immune response resulting from an offspring's exposure to the maternal immune system as a fetus and infant, Burlingham said. Former UW faculty member Ray Owen first reported the tolerance resulting from the maternal-fetal immune reactions in 1954.
"The findings support the hypothesis that cells and antigens of the mother change the antigen-specific reactivity of the fetal immune system and promote a long-lasting form of tolerance to later antigen challenge in the adult," Burlingham said. The relationship is complex, however. Burlingham's team found that kidneys from siblings with maternal immune traits were far more likely (more than 80 percent) to have early episodes of rejection.
The reported research began when Burlingham and the late Alan Grailer, also a UW transplant scientist, wondered why a young kidney recipient showed little sign of rejection long after forgoing strong anti-rejection drugs. Grailer found that the patient's blood contained circulating white blood cells derived from his mother, who was his kidney donor.
Through experiments, Grailer determined that a drastically outnumbered population of donor white blood cells coated with maternal antigens was able to suppress the recipient's expected immune response, creating a unique tolerance for the transplanted organ.
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